PB1725: INTERNATIONAL LEUKEMIA TARGET BOARD - A PLATFORM TO DISCUSS AND PRIORITIZE TARGETED TREATMENT OPTIONS FOR PATIENTS WITH RELAPSED/REFRACTORY PEDIATRIC HEMATOLOGICAL MALIGNANCIES (ILTB) – ITCC 107
Authors: Uri Ilan, Judith M. Boer, Birgit Burkhardt, Frederik van Delft, Shai Izraeli, Jan-Henning Klusmann, Barbara De Moerloose, Pablo Velasco, Julie Irving, José Luis Fuster, Dániel Erdélyi, Andreas E Kulozik, Dirk Reinhardt, Michel Zwaan, Monique L. den Boer
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Hematological malignancies represent one third of pediatric cancers. Long term cure rates exceed 80%. However, refractory and relapsed (r/r) disease occurs in approximately 15% of ALL, 25-30% of AML and 15% of lymphoblastic lymphoma patients. Several European pediatric personalized medicine programs (e.g. iTHER, INFORM and MAPPYACTS) apply deep molecular profiling of r/r disease to identify molecular events that can potentially improve patient outcome through matched targeted treatment. Since only ~10% of profiled patients are diagnosed with a hematological malignancy in these programs, information about targeted options in this population is limited. In addition, from those being profiled and discussed, only ~10% received targeted therapy. Aims: The international leukemia/lymphoma target board (iLTB) brings European experts together to advise the treating physician on the best possible treatment option. This is done by translational interpretation of molecular information, surface antigen expression and drug sensitivity testing when available, and subsequent prioritization of the actionable events and treatments, with the final aim to facilitate enrollment in clinical trials and/or collect real world treatment data. Methods: We developed the terms and conditions for an effective iLTB with various stakeholders from several European countries, resulting in a decision tree that incorporates molecular events, surface antigen expression and drug response profiling data. Results: In weekly iLTB virtual meetings, the integrated information obtained on site is discussed by the treating physician and a panel of international experts (molecular biologists, disease and clinical trial experts). Based on the patient’s treatment aim, treatment history and actionable events, the discussion within the iLTB results into a prioritized peers’ advice of best treatment options which is then communicated directly to the treating physician. The panel also share their experiences with new agents which are not yet available in clinical trials and/or are only applied in adults with similar disease. With the patients discussed so far, it is our experience that this advice can include combinations of known chemotherapeutics with targeted drugs, immuno-therapeutics and/or referral to clinical trials open for the specific indications or associated compassionate drug programs. After discussion, the study registry captures real-world data on treatment decisions and documents treatment outcome by a three-monthly follow-up. We expect to discuss 50-70 r/r hematological malignancy patients or high-risk patients with no standard of care each year. Summary/Conclusion: The iLTB advice, as well as monitoring follow-up on treatment decisions and outcome of patients, will increase our real-world knowledge about factors contributing to referral to open trials and compassionate use/off-label drugs of r/r patients. In addition, facilitating referral to targeted treatment/trials may increase accrual rates for such trials and monitoring compassionate use/off-label use may generate signals to develop new trials for this rare population of r/r cases. The iLTB registry will yield estimates of frequency of lesions for which no pediatric clinical trial yet exists, and will identify the reasons why some patients cannot be enrolled in clinical trials. All the above, will contribute to the improvement of clinical prospects for children, adolescents, and young adults with a r/r hematological malignancy. Keywords: Acute leukemia, Targeted therapy, relapsed/refractory, Children